nri medical college & gh, nrias information broucher.pdfas per the sop (standard operating...

NRI MEDICAL COLLEGE & GH, Chinakakani, Guntur (AP)-522503

Email.ID - [email protected] http://www.nrias.net/ethics.php

Some useful Hints

Information brochure for IEC-NRI Medical College & GH 1/42

mailto:[email protected]://www.nrias.net/ethics.phpDr MC DASRectangle

CONTENT Sl No Topic Page

1 Some useful Hints & Ethics 3

2 Application form 4

3 Protocol & Department scrutiny 10

4 Sample protocol 18

5 Reference in Vancouver style 22

6 Basic Biostatistics 24

7 Analysis 27

8 Standard operating procedure (SOP) of IEC, ICMR, New Delhi 34

9 Further reading on ethics 41


Action without a vision just passes time.

Vision without action is just a Dream.

Action and Vision can change the world

Ethics

It is a mistake to view ethics as an external, authoritarian imposition of regulations or possibly arbitrary constraints on the process of clinical research.

It is a practice of philosophy in day-to-day life and way of thinking and behavior – a matter of self-consistency and self-governance.

When do Ethics come in?

Before : Is the study needed and if so is it well planned? During : Protection of the subject’s dignity. After : Monitoring and Results, Publication.

No one / study is above ethics. All studies involving human subjects / Animals.

Prospective / retrospective Volunteers / patients Ayurvedic / modern Drugs / procedures Marketed / new drugs

WHO estimate that 65-80%of the world population use traditional medicine as their primary

health care. Traditional therapies based on Intuition or Experience of Experiment?

Quackery needs research A scientific a treatment may not hold its place in the market, if there is

no demand for it. Grossest quackery cannot be kept out of market if there is demand.

Traditional Medicine Needs Documentation

(In English modern scientific literature) It is not written, it did not happen? Document what happened as well as what did not happen.

* * *


Dr MC DASText Box Some useful Hints

To The Convener, IEC-NRI Medical College & GH, Chinakakani, Guntur, Project Title: Department: (Place of study) Purpose of the study:- *Dissertation/ Paper/ STS Principal Investigator

Name : Affiliation : ___ Year UG/PG student*/ Asst*./ Assoc.* Professor, (*Strike out which are not applicable) Department of_______________________, NRI Medical College & GH Email : Mobile .No :

Co-Investigator(s)* / Guide* (in case of Dissertation) (*Strike out which is not applicable) Name : Affiliation : Email :

Duration of the study :

Sponsors (if any with details) :

Approval from any other ethics / regulatory committee (if required) :

I/We shall follow the Good Clinical Practice guidelines and the approved protocol in conducting the research project. Further I/We declare that any sort of inclusion of text or Pictorial material which amounts to Plagiarism will be avoided.

Signature of the Investigator (s)

The proposal has been verified as per the requirement mentioned in the information brochure and forwarded to the IEC, NRI Medical College & GH, for approval. Synopsis of the project, Informed consent form, Case record form and Study flow chart are enclosed. Signature of the Guide for dissertation Signature of the HOD (With full name and rubber stamp) (With full name and rubber stamp)

“For information & Not to be typed” The application form is to be neatly typed with Times New Roman, 12 font size. The original is to be signed in each page by the investigator and properly numbered for page as shown. A soft copy of the proposal in word format to be mailed to [email protected]

(For IEC office use) Proposal No. Date:

Not to be typed in the application To be submitted to Dr. Muralidhar Reddy, Professor, Anatomy Dept. NRIMC & GH. (1) Original copy signed by PI in each page with 9 sets of Photostat copies (2) A soft copy in MS word format to be mailed to [email protected]


Dr MC DASText Box Application form

Version : 1.0 Page 2 of 5

SYNOPSIS Title: Principal Investigator: Department & Institution INTRODUCTION : *Briefly introduce the topic in 5 to 6 lines.

*Specific aim and objectives of the project. REVIEW OF LITERATURE: The review should not exceed one page. Briefly review the relevant earlier studies in running text with citations. A list of reference

is to be included in Vancouver style at the end of the synopsis. MATERIAL & METHODOLOGY:

*Describe the source of the subject :-

*Sample size / duration of the study:-

*Inclusion and exclusion criteria point wise.

*The procedures to be followed in the study (in brief):-

*Mention the potential risk in the study and the probable benefits of the study (if any):-

STATISTICAL ANALYSIS: *Mention the type of data to be collected.

*Exact statistical tests to be employed for analysis.

*Mention the level of significance.

REFERENCES : *Mention at least six references already cited in review in Vancouver style to support your project.



STUDY FLOW CHART

Title: Principal Investigator: Department & Institution:

*Recruitment of the subject & Enrollment

Selection of patients as per the inclusion-exclusion criteria

*Making study groups

*Study Procedures

Data collection

Statistical analysis

Conclusion

*Recruitment & enrollment of patient or volunteer require advertisement and payment. Is it true for your study? If not omit these points.

Not to be typed Can be modified to suit your objective.

*Consider if these points are required for your protocol



Confidential

ID No. ______ INFORMED CONSENT FORM (ICF)

Title: Principal Investigator: Department & Institution I, -------------(Name)-------------, aged about -------Years, a resident of --------------------------- village of --------------------------- district, have been detailed about the procedure. I know the benefit and risk of the said research project. I on my own will, agreed to participate in this study. I understood that my identity will not be disclosed and I can withdraw from the study at any point of the time without assigning any reason. My withdrawal from the study will not affect my ongoing treatment. ----------------------------- --------------------------------------------Signature of the witness if necessary Signature of the participant or Gurdian

IN LOCAL LANGUAGE

I, -------------(Name)-------------, aged about Years, a resident of village of district, having detailed the procedure, I know the benefit and risk of the said research project. I on my own will agreed to participate in this study. I understood that my identity will not be disclosed and I can withdraw from the study at any point of the time without assigning any reason. My withdrawal from the study will not affect my ongoing treatment. ----------------------------- --------------------------------------------- Signature of the witness if necessary Signature of the participant or Gurdian

The meaning of English and Telugu version of consent form must be same.

Not to be typed

The IFC form can be modified to suit your objective.

The IFC form may contain all the information like: Mob. No.; address of the patient; Bed No.; IP or OP No.; Admission date; Medico legal Case No and other details of the patient but required for the study; as it is confidential.



ID No. ______ CASE RECORD FORM (CRF) Title: Principal Investigator: Department & Institution: Design the rest of the form as per your plan of study to include all the necessary data for your project keeping the following points in mind- It must be brief and tailor made. No disclosure identity of the subject by any means.

Not to be typed Must be designed to suit your study. Preferably expected to be brief & objective. No disclosure of participants detail which may lead to disclosure of identity. Instead of address you may think of- Urban/ rural/ Semi-urban It must be more objective and study related e.g Family H/o or educational status is vague term. Instead you may consider:-

Educational status – Illiterate / Literate / Graduate / Professional Family H/O - DM Yes/No/Don’t know BP- ____ / ___ mm of Hg Pulse___/Min

Signature of the person collecting the data


Forwarding letter

The project entitled……………………………………………….. to be carried out by Dr……………..…………….. under the guidance of Dr………….…………………… , _________________Professor Department of ________________has been scrutinized and cleared by the Departmental committee.

As per the SOP (standard operating procedure) of the Institutional Ethics Committee (IEC-NRI Medical College & GH), the project has been reviewed for the following elements:-

1. Scientific design and conduct of the study. 2. Approval of appropriate scientific review committees. 3. Examination of predictable risks / harms. 4. Examination of potential benefits. 5. Procedure for selection of subjects in methodology including inclusion /

exclusion, withdrawal criteria and other issues like advertisement detail as required.

6. Management of research related injuries, adverse events. 7. Compensation provisions, if any 8. Justification for placebo in control arm, if any. 9. Availability of products after the study, if applicable. 10. Patient information sheet and informed consent form in local language.

Mention NA when any point is not required

11. Protection of privacy and confidentiality. 12. Involvement of the community, wherever necessary. 13. Plans for data analysis and reporting. 14. Adherence to all regulatory requirements and applicable guidelines. 15. Competence of investigators, research and supporting staff. 16. Facilities and infrastructure of study site(s). 17. Criteria for withdrawal of patients, suspending or terminating the study if

required. The project proposal is found satisfactory in all the above aspects [1-17] and being recommended to the IEC-NRI Medical College &GH for ethical clearance. This is also being certified that the proposal is not containing any text or pictorial material(s) which amounts to plagiarism. Signature of Guide for students / Signature of HOD Signature of PI for faculty (with full name and seal) (With full name)


Be brief but informative

INSTITUTIONAL ETHICS COMMITTEE NRI MEDICAL COLLEGE & GH,

Protocol is the blue-print of a clinical research project. Protocol designing is the most critical step in the entire clinical research process. Protocol is a document, definitely required by IEC, for approval of any research to be conducted in this institution. It is a written document to ensure transparency in Medical research. It should describe how an experiment would be implemented. After the protocol is finalized and approved, the Researchers should stick to the approved protocol. Any change must be re-approved through same process and is time consuming. So ‘write what your want to do & do what your have written’. Hence it is important that protocol is written after carefully planning the research project. Protocol planning process must take into consideration the following

Why? (Relevance of study) What questions will be answered? (Aim &Objectives) How will these questions be answered? (Plan of Study /Method) Measures to avoid bias and error? (Study design) How will the results be measured any analysed? (Outcome and statically

analysis). Possible difficulties and how to deal with them? Practical considerations-Resources-time available, budget vs. cost of study,

availability of patients, trained investigators and appropriate facilities? CRITICAL ELEMENTS OF PROTOCOL (Use this as check list)

1. TITLE Name of the trial (title) Name and designation of : Principal / Chief Investigator Guide Co-investigators in case of Interdisciplinary or Inter institutional

Collaborative research Sponsor’s medical expert Sponsor’s trial monitor Trial site(s) Table of contents of protocol (if protocol is elaborate)

2. INTRODUCTION

Background information Name and description of the investigational product. Summary of findings from nonclinical studies that potentially have clinical

significance and from relevant clinical trials.


Dr MC DASText BoxProtocol & Departmental srutiny

Summary of known and potential risks and benefits to human subjects. Justification of route of administration, dosage, regimen, treatment period. Description of the population to be studied. References to literature. Disease condition/ Standard therapy limitations. Likely advantages of new therapy.

3. OBJECTIVES

Formulation and expression of the study objective/s is the foundation of protocol development. This will determine type and design of study, sample size, interventions, methods of analysis . Objectives should be A clearly defined,. Single main question / hypothesis (primary objective/s) Secondary questions may be included. But are subordinate (Secondary

objective/s) 4. DESIGN

Prospective or retrospective Randomization ensures comparability of test groups minimizes selection

bias. Blinding-subject, evaluator, investigator-minimizes biased outcomes. Control group- placebo, no treatment, comparative treatment and different

doses of test drug.

5. SELECTION OF SUBJECTS Who? Healthy volunteers, patients? Age & Sex? How many? Sample size? Sufficient number to get valid results Not more that necessary to avoid wastage of resources Influenced by Disease to be investigated-common, rare Objective/s of the study Study end points Expected magnitude of the treatment effect Variability of the data Specified (small) probability of error (power of the study) Subsets of population or secondary end points From where will subjects be recruited? Hospital out-patients, in-

patients, G.P.Practice ? Criteria for eligibility:- To ensure enrollment of right type of

subjects (target population for the therapy). a) Inclusion criteria – Define medical status with regard to condition /

disease under study. Patient characteristics Disease Characteristics Previous administered treatment Environment and other factors Screening results


b) Exclusion criteria – Based on safety considerations, anything else that will interfere with measuring effect of therapy.

Concurrent illness Concomitant therapy Pregnancy and Lactation Contra-indication to therapy End organ damage Noncompliance

6. OUTCOME MEASURES :- Includes efficacy & safety assessment. Study and points chosen to assess drug effects e.g.BP, Quality Of

Life (QOL), Pain relief. Study should be clinically relevant and based on principle objective

of the study Should be defined prospectively Methods of observation and quantification must be specified Objective/ subjective methods of observations should be validated

accurate, specific, sensitive, reproducible. Procedure for documentation of ADRs and intercurrent illnesses Follow up of adverse events

7. WITHDRAWAL CRITERIA – in case or RTC or drug trial Rules for withdrawal must be pre-defined and applied without bias Define procedures to handle protocol violators and dropouts,

withdrawals,. Therapy failures.

8. STUDY PLAN / INTERVENTIONS Procedures and schedules for treatment, examination, investigation

should be clearly stated. Dosage, formulations, schedules., duration of drug treatments. Must

be specified. Under what circumstances drug administration will be modified /

discontinued Concomitant therapy permitted must be specified

9. STATISTICAL ANALYSIS - Prospective plan for data analysis must be specified in protocol

Choice of statistical tests depends upon type of data/study objective Level of significance of outcomes must be stated Plans for interim analysis, if any should be specified Patients who will be excluded from analysis must be pre-defined.

10. ETHICAL REQUIREMENTS Informed consent form in writing both English & local language Protection of safety and rights of human subjects Voluntary withdrawal Patients information sheet about trial (Optional) Procedures for written informed consent(Optional)


11. CASE RECORD FROM (CRF) Must capture required, relevant, accurate and analyzable data

It is tailor-made to suit the data collection Should not contain Name, OP/IP/Regd. No. or bed number, address,

date of admission/discharge, which may reveal identity of patient. Address can be included as Rural / semi-urban / Urban etc.. Confirms to protocol requirement Checks protocol adherence Facilitates data transfer and processing As per regulatory requirements

12. ADMINISTRATIVE PROCEDURES (If required) Medication storage and dispensing Packaging, labeling and coding for drugs and placebo Accounting procedures Protocol amendments Early trial discontinuation Insurance, compensations and reimbursements Publication policy-matters of news paper advertisements for patients’

recruitment of trial must be approved by IEC, press release for interim results should be carefully evaluated

Specific circumstances for code breaking and further management Audit

13. SPONSORSHIP / FUNDING DETAILS – self sponsored or by any institution or applying for any sponsorship must be mentioned

14. Reference Minimum six & maximum of ten, most relevant references should be given in Vancouver style with proper citation..

ENCLOSURES: (MUST ATTACH)

Patients information sheet (Optional for dissertation & paper work) Informed consent form (ICF) in English / Telugu (Specimen enclosed) Case record form (CRF) News paper publication matter for subjects recruitment (if any) Funding details of Sponsor (if any) Study flow chart Permission letter of other institutes (if any)

SPECIAL CONSIDERATIONS (CLINICAL TRIALS ON TRADITIONAL MEDICINE).

Define treatment/s and indication/s clearly so that other researchers can produce them reliably.

Ensure quality control and standardization of study drugs When active principle is known prepare formulation as per GMP standards Make all trial supplies at the beginning to take care of batch-to-batch

variation. Involve Traditional Medicine Doctor as co-investigator.


Optional for thesis

INSTITUTIONAL ETHICS COMMITTEE NRI MEDICAL COLLEGE & GH,

PATIENTS’ INFORMATION SHEET (PIS)

Before requesting an individual’s consent to participate in research, the investigator must provide the individual with the following information in the language he/ she is about to understand which should not only be scientifically accurate but should also be sensitive to their social and cultural contexts :

1. Title of the research project 2. The identity of the research teams with address and phone number of contact

person/s 3. The aims and the methods of the research 4. The expected duration of the subject’s participating 5. The benefits that might reasonably be expected as an out come of research to

the subject or to others 6. Any alternative procedures of courses of treatment that might be as

advantageous to the subject as the procedure or treatment to which she/he is being subjected

7. Any foreseeable risk or discomfort to the subject resulting from participation in the study

8. Right to prevent use of his/her biological sample (DNA, Cell-line, etc) at any time during the conduct of the research

9. The extent to which confidentiality of records could be maintained 10. Responsibility of investigators 11. Whether free treatment for research related injury be the

investigator/institution will be provided 12. Whether any compensation / reimbursement/insurance cover for

participation or risk involved 13. Freedom of the individual to participate and to withdraw from research any

time without penalty or loss of benefits which the subject would otherwise be entitled to

14. Foreseeable extent of information on possible current and future uses of the biological material and of the data to be generated from the research and if the material is likely to be used for secondary proposes or would be shared with others., clear mention of the same

15. Risk of discovery of biologically sensitive information 16. Publication if any including photographs and pedigree charts

Each participant of clinical trial should be given patients information sheet. However in ordinary research one may combine patients information sheet and informed consent form in one format (In both English & Oriya). If the patient demands informed consent form please prepare second original patient.


Informed Consent Form (ICF)

“Title of Project_______________________________________________________”

CONFIDENTIAL ID. No. ________

“Investigator’s Name___________________________________________________” I_______________________________ aged______ years resident of ___________ fully aware of the work and the procedures of the research, in my Free will ; without any pressure or incentive in any kind; hereby give my consent (as well as consent on behalf or patient Named ___________________Aged years as his/her_______________relative) to be included as subject in the said clinical study. I have clearly understood that I have the right to withdraw from the study at any time with out assigning any reason. My information and identity will be secret I acknowledge the receipt of “patient’s Information sheet” and also the doctors have informed me about this research project suitably and sufficiently to my satisfaction. I agree to let my X-ray. Other investigations, photographs and blood samples be drawn as required. I agree to take necessary medicines regularly as per this trial doctor’s instructions and shall not mix any other treatment during the period of this trial. I shall report to hospital or other place where called on given appointment dates and time. I shall inform the doctors for any adverse effects or unusual symptoms noticed by me. I shall co-operate with doctors and paramedical staff in all respects. I permit to publish the results of my participation in this study. I shall not be given any reimbursement of compensation. I have been informed of my right to opt out of his research project at any time without giving any reason for doing so. I hereby record my consent for participation in the said trial. 1._______________________ ___________________ ____________ _________ Patient’s Name Signature/Thumb print Date Time Or_________________________ _____________________ _____________ __________ Name of the person providing consent Signature/Thumb print Date Time 2.____________________________ _______________________ ______________ ___________ Witness Name Signature/Thumb print Date Time 3.____________________________ _______________________ ______________ ___________ Investigator’s Name Signature/Thumb print Date Time PLEASE RECORD THE PATIENT’S ID BELOW AFTER RANDOMIZATION PATIENT’S ID :

Center No. Randomization No.

* strike out matter in bracket if not applicable.


Specimen Informed Consent Form (ICF)

CONFIDENTIAL ID. No.

INFORMED CONSENT FORM Title: Principal Investigator: Department & Institution I, -------------(Name)-------------, aged about -------Years, a resident of --------------------------- village of --------------------------- district, have been detailed about the procedure. I know the benefit and risk of the said research project. I on my own will, agreed to participate in this study. I understood that my identity will not be disclosed and I can withdraw from the study at any point of the time without assigning any reason. My withdrawal from the study will not affect my ongoing treatment. ----------------------------- --------------------------------------------- Signature of the witness Signature of the participant / Gurdian

IN LOCAL LANGUAGE

I, -------------(Name)-------------, aged about Years, a resident of village of district, having detailed the procedure, I know the benefit and risk of the said research project. I on my own will agreed to participate in this study. I understood that my identity will not be disclosed and I can withdraw from the study at any point of the time without assigning any reason. My withdrawal from the study will not affect my ongoing treatment. ----------------------------- --------------------------------------------- Signature of the witness Signature of the participant / Gurdian

1) Informed Consent Form (ICF) may be modified as per your need. 2) It may contain all the personal detail of patient or participant like

address, Mob No, OP No or IP No and others which may be subsequently required in your study


Specimen copy

CASE RECORD FORM (CRF) ID No____

Project Title “______________________________________________________”

Investigator_____________________ Department._______________ Tel.No______

NRI MEDICAL COLLEGE, Chinakakani, Age in years____ Sex – M/F Reporting Date_________________ Diogonosis_____________________Drug and dose____________________________

Date Clinical findings Score

Adverse events monitoring

Efficacy parameters Safety parameters Subjective Lab.Tests Subjective Lab.Tests 1 2 1 2 1 2 1 2

1st visit

• You may use separate case record form for each visit to avoid bias findings of earlier visit. • Design detail case record form to fulfill the needs of your protocol.

* Design the CRF to suit the data you want to collect.

* Be specific and include those points absolutely requied for your work

* No details of patient in CRF like case No, IP No or OP NO.

* All these details can be recorded in Consent form (ICF).


SAMPLE PROTOCOL IEC-NRI Medical College & GH, Chinakakani, GUNTUR.(AP)

“CLINICAL STUDY OF FORMULATION ‘X’ IN PATIENTS WITH

CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)” INTRODUCTION : COPD is one of the most common lung disorde3rs following pulmonary tuberculosis1. It accounts for 25 to 30 % of cases in most non-tubercular chest clinics2. The disease is equally prevalent in rural and urban areas of India affecting more of maltase as co, pared to females/ Smoking, increasing pollution. Followed by occupational exposures are the main causes of (COPD). The main goals of therapy in COPD cases are to reverse to the maximum extent possible airway obstruction and to provide symptomatic relief; to prevent or retard the progressing of the disease; to treat the complications and to rehabilitate the individual. The drugs which are routinely used in the management of a COPD case are antimicrobials, 2 agonists, Methyl-xanthenes, anti-cholinergics, corticosteroids, antibiotics and mucolytics3. The rationale behind the use of mucolytics is that they may decrease sputum viscosity, increase sputum clearance and perhaps improve mucociliary transport thus improving air flow limitations. The use of mucolytics alone has failed to show significant improvement in symptoms of pulmonary functions in subjects with chronic bronchitis4. OBJECTIVES: To evaluate the efficacy of formulation ‘X’ when uses as an add on therapy in patients with COPD and Brochiectasis. DESIGN: Randomized Prospective study NUMBER OF SUBJECTS: 25 patients in each group INCLUSION CRITERIA :

Patients of either sex over 18 years of age Patients diagnosed to be having COPD Chronic Bronchitis-as defined by WHO Emphysema Patients of Brochiectasis Patients showing partial reversibility in FEVI

(Change in FEVI of less than 15% after the administration of Salbutamol) Patients having exacerbation due to infection Patients who can give written informed consent Patients who are ready to come for follow up

EXCLUSION CRITERIA : pregnant of lactating women Patients not able to perform Pulmonary Function Test Patients on high doses of steroids Patients in cardiac failure Moribund patients Patients with chronic ailments such as Rheumatoid Arthritis etc Patients with abnormal liver/kidney functions


INFORMED CONSENT : The Principal investigator will explain the participant detail procedure and merit, demerit of the study, and will ask to sign the consent form once the participant has understood the contents clearly. It would be informed to the participant that he/she is free to withdraw from the trail at any moment without providing the reason to do so. STUDY DRUGS : COMPOSITION : Formulation ‘X’ DOSE : 1 Tablet twice a day. METHODOLOGY : All consecutive patients attending the OPD will be screened and will be recruited n the study if they satisfy the inclusion/exclusion criteria (from the eligibility form) of the study, following which their written informed consent will be procured. Once the patient is recruited in the study, baseline assessments will be performed in which past history of the patient relating to last six months with respect exacerbation, whether the patient was hospitalized, or whether the patient had to see the doctor, the number of days the patient had to remain away from work due to exacerbation will be noted, Even the detail drug history of the patient will be noted. Obstetric and menstrual history will be recorded in case of females. Details of smoking. Tobacco and alcohol consumption will also be taken. The patient will then undergo a general examination wherein the temperature, pulse rate, respiration rate, the blood pressure of the right arm in the supine position will be determined. A systemic examination will be performed and any relevant findings will be noted. Each patient will also have to undergo hematological, serological and biochemical evaluation at the beginning and at the end of the trial. The baseline assessment, parameters such as cough frequency, cough severity, cough discomfort, chest discomfort, sputum quantity, sputum thickness as felt by the patient will be graded. Breathlessness, ronchi and rales will also be evaluated. The patient will then gave to undergo a pulmonary function test and the arterial blood gas measurements will also be performed. Details of exacerbation, if the patient had to be hospitalized, if the patient had to contact the doctor, number off days the patient had to remain away from work due to exacerbation and hospitalization will be noted. The gradation of the parameters is mentioned below in the parameters for evaluation. Once the diagnosis and actiology is confirmed the patients will be randomized (as per the random allocation list) to receive one of the treatments which is coded as either Treatment A or Treatment B. The patient will either receive the active drug Formulation ‘X’ or the Placebo. The treatment will be administered for a period of six months and the patients will have to come for follow intervals wherein the necessary parameters as enlisted in the CRFs will she noted. For each patient return tablet count will be made as well as compliance to the treatment protocol will be ascertained during each follow-up visit.


Every patient will also be given an ID card in order to ensure that the same investigator throughout the trial assesses the patients and also to facilitate recognition of the trial patients during the visits. PARAMETERS FOR EVALUATION: The following parameters will be evaluated at each follow up:

1. Fever (Temp in degree celcius.) 2. Cough

a. Cough frequency b. Cough severity c. Chest discomfort

Cough frequency severity and discomfort will be graded on VAS for both day and night. A standard scale 10 cm long will be used by the patient to grade the parameters of cough. Patients will have to grade cough frequency severity and discomfort as the experience during the day and night. They have to place a mark on the 10 cm line which will best describe their symptoms. 0 cm will corre3spend to no cough and 10 cm will correspond to maximum or sever symptom as felt by the patient.

B) Chest discomfort C) Sputum quantity D) Sputum thickness

Chest discomfort, sputum quantity and a sputum thickness will be graded as Absent. Mild, Moderate or Server.

3. BREATHLESSNESS : It will be graded as follows : GRADE

Normal 1 Able to walk with normal person of his own age. 2 Sex and build on level but cannot keep up on hills or stairs. Unable to keep up with normal persons on the level but can 3 Walk long distances at his own speed. Unable to walk more than 100 yards on level before dyspnoea 4 Make him stop. Unable to walk more than few steps without dyspnoca and 5 Becomes breathless even when washing or dressing.

4. RALES : Areas covered will be R & L mammary, R & L axillary, R & L interscapular and R & L infrascpular.

It will be graded as Absent, Inspiratory or Both (Inspiratory or Expiratory) 5. RHONCHI : Areas covered will be R & L mammary, R & L axillary, R & L

interscapular and R O infrascapular. It will be graded as Absent, Inspiratory or Both (Inspiratory or Expiratory) 6. EXACERBATION is defined as increase in breathlessness leading to increase

in the dose of bronchodilator and / or. a. Increase in quantity of sputum and / or b. Increase in purulence of sputum requiring antibacterial agents

Number of exacerbations since last visit will be noted.


7. Need for hospitalization will be noted as Yes or No. If yes then how many times the patient was hospitalized since last visit, will be recorded.

8. If the patient was not hospitalized then the number of times the patient contacted the doctor due to deterioration in his/ her respiratory symptoms will also be noted.

9. Number of days for which the patient had to be away from work due to above parameters.

10. PULMONARY FUNCTION TEST (It will be performed at 0, 3 and 6 month)

FVC FEVI FEVI FVC PEFR

FREQUENCY OF MEASUREMENT : The study will go on for 6 months. All the above clinical parameters will be evaluated at every monthly interval. Pulmonary function test and Arterial blood gases measurements will be carried out at the beginning of the study, at the end of the 3rd month and at the end of the study, General examination will be cared out at the baseline and at every monthly visit. The hematological, serological and biochemical parameters will be recorded at the baseline and repeated at the end of the trail. ADVERSE EFFECTS : Any adverse effect, if at all, occurring during the course of the study will be noted and the attending physician will opine whether the adverse reaction could have occurred due to the treatment administered. If the adverse reaction is a serious one, then the monitor should be contacted immediately and he will be available for comments and SOS action even at his residence. All the relevant data of the patient should be entered in the case report form provided. Any patient’s data if not available for evaluation will be concluded as dropout and if the treatment is to be changed due to change in physical condition of the patient then also the patient will be dropped out from the study. Under no circumstances, the patient will be compelled to continue with the study against their will. STATISTICAL ANALYSIS: Mention details of statistical test to be applied with level of significance. References (Vancouver style): 8 to 10 relevant reference with their citation in text of protocol should be given.


Reference in Vancouver style 1. Park K. Park’s text book of preventive and social medicine.

20th ed. India: Banarsidas Bhanot publication; 2009. p 13.

2. Sharpe MC, Potts SG. Medical psychiatry. In: Nicholas Boon A,

Nicki Colledge R, Brian Walker R, John Hunter AA, editors.

Davidson’s principles and practice of medicine. 20th ed. India:

Elsevier; 2006. p 228.

3. Goel DS, Saldanha D, Pawar AA. Depression and bipolar

disorders. In: Madhur Gupta, Sheela Tejwani, editors.

Contemporary perspectives on clinical pharmacotherapeutics.

1st ed. India: Elsevier; 2006. p 153.

4. Mishra S, Khanna VK, Vikas kumar. 5 HT2A receptor binding

and antidepressant studies on anximin, a poly herbal

formulation. Pharmacologyonline [Online serial] 2008; 2: 379-

389. Available at: http://www.unisa.it/download/1966_10305_

874923766_34_Vikas.pdf. Accessed September 15, 2009.

5. Jaanus Harro. Animal models for better antidepressants: can

pathogenic approaches make a difference? Preclinica [Online

serial] 2004; 2(6): Available at :http:// www.preclinica.com/

content/articles/1104/14.pdf. Accessed Auguest 26, 2009.

6. Allan Kalueff V, Pamela S, Gallagher, Dennis Murphy L. Are

serotonin transporter knockout mice depressed? Hypoactive

but no anhedonia. Neuroreport 2006; 12(17): 1347-1351.

7. Akhilesh Jain, Dhaka LC. Mood disorders: Differential

diagnosis. In: Vyas JN, Nathawat SS, Manilal Gada and


Razdan VK, editors. Essentials of postgraduate psychiatry. 1st

ed,vol.1. India: Paras publication; 2005. p 587.

8. Vyas JN. Mood disorders: Clinical features. In: Vyas JN,

Nathawat SS, Manilal Gada and Razdan VK, editors. Essentials

of postgraduate psychiatry. 1st ed vol-1. India: Paras

publication; 2005. p 564.

9. Vyas JN, Dinesh Tyagi. Mood disorders. In: Vyas JN, Niraj Ahuja editors. Text book of postgraduate psychiatry. 2nd ed vol-

1. India: Jaypee publication; 2000. p 191-196. 10. Sharma HL, Sharma KK. Principles of pharmacology. 1sted.

India: Paras publications; 2007. p 469-470.

11. Kandi CS, Metkar BR, Kasture US, Kasture SB. Effect of

serotonergic agents on amphetamine induced stereotypy.

Indian J Pharmacol 1998; 30: 334-38.

12. Singh H, Goyal BL, Singh P. Study of neuro-excitatory features

during diazepam withdrawal reactions and their correlation with

brain gamma amino butyric acid levels. Indian J Pharmacol

1998; 30: 267-270.

13. Barden N. Implication of the hypothalamic–pituitary–adrenal

axis in the physiopathology of depression. J Psychiatry

Neurosci 2004; 29: 185–193.

14. Pav M, Kovaru H, Fiserova A, Havrdova E, Lisa V.

Neurobilogical aspects of depressive disorder and

antidepressant treatment: role of glia. Physiol Res 2008; 57:

151-164.


Basic biostatistics Observations are known as data.

Only grouped data are to be compared.

Isolated event or a single value can not be compared.

Real and chance error can be differentiated.

No need for comparison

Mean weight of two groups of sphere and mean

diameter of two groups may be compared

Objectives

Appreciate the importance of statistics in research

Understand the principles of selecting a statistical test

Gain insight into the necessity for eliminating bias in experimental work

Use and apply some of the commonly used statistical tests and methods

Report statistical methods correctly in scientific publications

Basics in Experimental Research

Continuous changes in Nature with change in time bring uncertainty and variability in each

and every sphere of Science. Even well known and tested principles and laws do fail with test

of time. We can not control or over-power the factor of uncertainty but can measure it in


terms of probability. This will differentiate a real variation from accidental or chance

variation.

Data (observations) one record in experiment may be dependent, independent or

derived. BP depends on drug used, BMI. So BP is a dependant data. Weight, height and

number of family members are independent data. BMI is calculated from height and weight.

So BMI is a derived data.

Data can be further divided as primary data which is collected directly by the observer. It can be secondary data, when the observation is not collected directly but indirectly. Observations of one researcher are used by another. Data published

can be used. Hospital records are used for secondary data.

Error and Bias No experimentation or observation can be totally free from errors and escape from bias. But

we must identify and recognize them for their elimination as for as possible or to control and

minimize the effect. Measurements even being valid, if lack in precision and accuracy,

irrespective of the magnitude or quantity of deviation from the intended measurement, are

called errors. One sided repeated errors or systematic errors are called bias. Selection or

allocation biases, measurement bias, instrument bias, inter & intra investigator or observer’s

bias, misclassification bias etc. are some of the frequently encountered bias. We know that

the techniques of blinding, randomization, replication, standardization, selection of

controls and to a great extent the experimental designs do help us to overcome some of them.

The clarity in knowing the variables of interest to be considered in a particular

study helps a lot in recruitment of research tools, techniques and methods to be used

during experimentation and use of statistical tests at the end of the study.

Measurement Scales


Each variable has its own limitation of measurement. A suitable nominal scale can just

classify most of the qualitative variables. Whereas, only for a few of such characteristics it

may be practical to put the classification in an ordered sequence by using an ordinal scale,

still the distance between two points is not the same. But numerical or quantitative variables

can always be measured either by interval scale or ratio scale. The interval scale is valid for

certain interval of the possible measurement, as in case of temperature the freezing and

boiling points of water have been the basis of scaling in absence of the knowledge of absolute

zero temperature. However ratio scale has an absolute zero such as weight, height, and pulse

rate etc. How sensitive we are at measurements or in making observation determines

precision in inference. A neonate can hardly differentiate between the father and mother but

an infant does. It is the wisdom and the sensitivity in measurement, which reveals that even

the atoms of an element are all different if we consider the flow of electrons. If we go to that

degree of sensitivity in measurement we find that even Nature is incapable of reproducing

two exactly similar objects or subjects. If we were in a position to utilize the information,

increasing the sensitivity in measurement would certainly be more revealing. But the

approach to exhaust all resources for having Nano-sensitivity in measuring the input variables

in contrast to Pico/micro-sensitivity used for measuring the output variables is wasting

resources without any gain.

VARIABLE ATTRIBUTE

DATA

Ht 145 Cm 152 .5 Cm Wt. 50 Kg 65.35 Kg Tall ShortLean Obese

Ht

Wt

Ht

Wt

Discrete


Scale of measurement and Type of data Continuous measurement Height in cm, Weight in Kg, Time in seconds is continuous

Ht may be 155,155.2, 155.8, 160

Weight in kg 55.5, 57.0, 57.8 etc

BP in mm of Hg

Thyroid status T3, T4 or TSH level

Discrete measurement Family size, Number of live birth, Number of patients cured

Family size can be 2,4,6 etc;

Height can be Tall, short, medium,

Weight can be normal, obese, over weight etc

BP Normotensive, Hypertensive, Hypotensive etc

Thyroid status Euthyroid, Hypothyroid, Hyper thyroid etc

Central tendency, Variation, Confidence intervals Central tendency – Mean, Median

Find out the mean for the interval data

Median is used for scores and ranks

Variation - SD, SE, Range

SD will be appropriate only if data are normally distributed (symmetric distribution).

Range includes the lowest and the highest values (eg. Dose of a drug : 10-25 mg/kg)

Confidence interval – CI or fiducial limits

Confidence limits are two extremes of a measurement within which 95% of observations

(values) would lie.

Analysis

Continuous data Discrete data

(Parametric test) (Nonparametric test)

t-test Chisquare-test

Z-test Sign rank test

Anova Kruskalwalis oneway ANOVA

Co-relation

Regression


The Chi Square Test The Chi square test is a non parametric test of proportions. It is used to test a hypothesis. If

the association between two variables is to be tested this test is commonly used. If the sample

size is small a corrective test -the Fisher’s Exact test can be used. The limitation of this test is

that it does not test the strength of association.

To compute this test a 2X2 table or contingency table has to be made. These tables are made

to test the association between a treatment and an outcome. The variables used for this table

are usually dichotomous e.g. death/survival; adverse effect present/absent. In case they are

not, the investigator can transform the values into dichotomous data by specifying a particular

threshold value and then computing what proportion of subjects fit above or below this

threshold. These tables are made to present data from cross sectional studies, case control

studies, diagnostic tests, RCTs etc.,

How to make a 2X2 table?

In a contingency table you must enter raw data, that is the exact number of subjects / animals

etc., – not percentages, means or fractions. The groups (treatment/control; exposure/no

exposure) are entered on the left side as rows, with the treatment group in the top row and the

control group in the second row. The outcome is entered as columns on the right side with

the positive outcome as the first column and the negative or no change outcome as the second

column. The columns and rows are also mutually exclusive. A particular subject or patient

can be only in one column not in both.

The following is a template of a 2X2 table

Outcome Exposure

Yes No

Yes

No

Example: Patients with symptoms of viral upper respiratory tract infection were divided into

two groups and given placebo or antihistaminics (AH). The result was recorded as

improvement or no improvement after 48 hours.

improvement no improvement Total

Drug / Intervention 58 442 500

Placebo/No intervention 67 423 490

Total 125 865 990


Student’s ‘t’ test Student’s ‘t’ test is probably still the most popular of all statistical tests. The test compares

two mean (average) values to judge if they are different or not. The Student’s ‘t’ test is the

most sensitive test for interval data, but it also requires the most stringent assumptions. The

variables/data are assumed to be normally distributed.

The following ‘t’ tests are commonly used :

1. One sample t test the mean (test) of a single group is compared with a hypothetical

value (control).

2. Paired t testwhen the ‘paired design’ is used, paired t-test is applied (eg. BP measured

before (control) and after (test) a drug administration in a single group of subjects)

3. Unpaired t test for comparing two individual groups (eg. Height of two groups of

subjects each)

The conditions for applying t test are as follows:

1. The sample must be chosen randomly

2. The data must be quantitative (measurable e.g. height, BP)

3. The data should follow normal distribution

4. The size is ideally 30, go for normal test.

‘t’ test will give unreliable results if the above conditions are not met.

Random Allocation http://www.random.org/integers/

To allocate subjects or animals to different groups, randomization is followed so that each

eligible individual in the population has the same chance of being allocated to a group. This

eliminates selection bias. Haphazard allocation cannot be called random. Random number

tables or computer programs can be used for random allocation. Simple randomization using


http://www.random.org/integers/

computer generated random numbers are used commonly. Sometimes simple randomization

may pose problems. For example, randomly allocated two groups may have a different

male:female ratio. If it is important to have equal number of males and females in all groups,

then one of the slightly complex randomization procedures such as block, stratified or cluster

randomization should used.

Significance Testing Null hypothesis (statistical hypothesis) states that there is no difference between groups

compared. Alternative hypothesis or research hypothesis states that there is a difference

between groups.

e.g. New drug ‘X’ is an analgesic - (Research hypothesis)

Null hypothesis H0 (A B) New drug ‘X’ is not better than a placebo (no difference between the drug and placebo) Alternative hypothesis H1 (A B => A > B or B >A) New drug ‘X’ is better than a placebo

Alpha is type 1 error and the acceptable limit is to be set. It is generally set at 0.05 (5%) and

not above. If the P value is less than this limit then null hypothesis (H0) is rejected and

alternate hypothesis (H1) is accepted i.e. the difference between groups is by chance but real.

If statistical test is a judge. The accused (= drug under investigation) is not guilty (= null

hypothesis) until the charges are proved. The judge’s decision depends on evidences (= data).

Calculation of the chances (P) of the evidence presented by the investigator (= researcher)

being false (= probability of difference observed between groups being spurious). If this is

< 0.05, then the accused is guilty (the difference between groups is significant). If P > 0.05,

the benefit of doubt to the accused (=the difference is not significant and the drug is thrown

out).

Choosing an appropriate statistical test There are various statistical tests. The characteristics of data will determine a suitable test.

The p value is calculated indirectly from a statistical table.

The following details may help - choosing a suitable test .

Significance tests can be divided into Parametric and Non-parametric tests. The former

includes t test, ANOVA, linear regression and Pearson correlation co-efficient whereas the

later includes Wilcoxan, Mann Whitney U, Kruskal-Wallis ANOVA, Friedman ANOVA and

Spearman rank correlation. Those variables which follow normal distribution can be

subjected to parametric tests and those which do not are suitable for non-parametric test. If

the aim is to find out the association between variable, correlation or regression tests should

be chosen; the difference between means or medians can be found out using other tests. If Information brochure for IEC-NRI Medical College & GH 30/42

more than two groups/means are compared ANOVA should be used. Significance test to be

used must be decided at the beginning of the study.

A study may need more than one test depending on the number and characteristics of

the parameters studied.

Always spend enough time and brain to choose a right test

Inappropriate test will lead to invalid conclusions.

Factors to be decided:- Aim of the study –

Parameter to be analysed -

No. of groups to be analysed -

Data type - [Continuous, Discrete, Rank, Score,]

Analysis type - [Comparison of means, Quantify association, Regression analysis]

Design - [paired or unpaired]

With the above information, one can decide the suitable test using the table given.

Calculating and Interpreting P

When the data are subjected to significance testing, the resulting value is called statistic. This

can be t (t test), chi (chi square), F (ANOVA) etc depending on the test used. This statistic is

used to find out the P value available from tables (statistics software can automatically

calculate the P value). If the P value is less than the cut off value (level of significance i.e

alpha error), it is considered that the difference between the groups is statistically significant.

When P is 0.05, the difference is considered statistically non-significant and it is concluded that

there is no difference between the groups or the difference is not detected.

Non-significant result can be due to two reasons :

1. There is really no difference between the groups.

2. The study is not powerful enough to detect the difference.

Hence, one should calculate the power to conclude whether there is no difference or the

power is inadequate. If the power is inadequate (

Critical Values of the χ2 Distribution

Area in the Upper Tail df 0.99 0.95 0.9 0.1 0.05 0.01 1 0.000 0.004 0.016 2.706 3.841 6.635 2 0.020 0.103 0.211 4.605 5.991 9.210 3 0.115 0.352 0.584 6.251 7.815 11.345 4 0.297 0.711 1.064 7.779 9.488 13.277 5 0.554 1.145 1.610 9.236 11.070 15.086 6 0.872 1.635 2.204 10.645 12.592 16.812 7 1.239 2.167 2.833 12.017 14.067 18.475 8 1.646 2.733 3.490 13.362 15.507 20.090 9 2.088 3.325 4.168 14.684 16.919 21.666 10 2.558 3.940 4.865 15.987 18.307 23.209 11 3.053 4.575 5.578 17.275 19.675 24.725 12 3.571 5.226 6.304 18.549 21.026 26.217 13 4.107 5.892 7.042 19.812 22.362 27.688 14 4.660 6.571 7.790 21.064 23.685 29.141 15 5.229 7.261 8.547 22.307 24.996 30.578 16 5.812 7.962 9.312 23.542 26.296 32.000 17 6.408 8.672 10.085 24.769 27.587 33.409 18 7.015 9.390 10.865 25.989 28.869 34.805 19 7.633 10.117 11.651 27.204 30.144 36.191 20 8.260 10.851 12.443 28.412 31.410 37.566 21 8.897 11.591 13.240 29.615 32.671 38.932 22 9.542 12.338 14.041 30.813 33.924 40.289 23 10.196 13.091 14.848 32.007 35.172 41.638 24 10.856 13.848 15.659 33.196 36.415 42.980 25 11.524 14.611 16.473 34.382 37.652 44.314


Critical Values of the t Distribution

2-tailed testing 1-tailed testing

" " df 0.1 0.05 0.01 0.1 0.05 0.01

5 2.015 2.571 4.032 1.476 2.015 3.365 6 1.943 2.447 3.707 1.440 1.943 3.143 7 1.895 2.365 3.499 1.415 1.895 2.998 8 1.860 2.306 3.355 1.397 1.860 2.896 9 1.833 2.262 3.250 1.383 1.833 2.821

10 1.812 2.228 3.169 1.372 1.812 2.764 11 1.796 2.201 3.106 1.363 1.796 2.718 12 1.782 2.179 3.055 1.356 1.782 2.681 13 1.771 2.160 3.012 1.350 1.771 2.650 14 1.761 2.145 2.977 1.345 1.761 2.624 15 1.753 2.131 2.947 1.341 1.753 2.602 16 1.746 2.120 2.921 1.337 1.746 2.583 17 1.740 2.110 2.898 1.333 1.740 2.567 18 1.734 2.101 2.878 1.330 1.734 2.552 19 1.729 2.093 2.861 1.328 1.729 2.539 20 1.725 2.086 2.845 1.325 1.725 2.528 21 1.721 2.080 2.831 1.323 1.721 2.518 22 1.717 2.074 2.819 1.321 1.717 2.508 23 1.714 2.069 2.807 1.319 1.714 2.500 24 1.711 2.064 2.797 1.318 1.711 2.492 25 1.708 2.060 2.787 1.316 1.708 2.485 26 1.706 2.056 2.779 1.315 1.706 2.479 27 1.703 2.052 2.771 1.314 1.703 2.473 28 1.701 2.048 2.763 1.313 1.701 2.467 29 1.699 2.045 2.756 1.311 1.699 2.462 30 1.697 2.042 2.750 1.310 1.697 2.457 40 1.684 2.021 2.704 1.303 1.684 2.423 50 1.676 2.009 2.678 1.299 1.676 2.403 60 1.671 2.000 2.660 1.296 1.671 2.390 80 1.664 1.990 2.639 1.292 1.664 2.374

100 1.660 1.984 2.626 1.290 1.660 2.364 120 1.658 1.980 2.617 1.289 1.658 2.358 4 1.645 1.960 2.576 1.282 1.645 2.327


MC DOSText Box* * *

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Standard Operating Procedures (SOPs) for Institutional Ethics Committee (IEC) of ICMR’s Headquarters Office, New Delhi,

INDIA

1. Objective: The objective of this SOP is to contribute to the effective functioning of the IEC at the Indian Council of Medical Research, Headquarters Office, New Delhi, India, so that a quality and consistent ethical review mechanism for health and biomedical research is put in place for all proposals dealt by the Committee.

2. Role of IEC

ICMR Headquarters IEC will review research proposals involving human subjects submitted by scientists of ICMR Headquarters Office, New Delhi to various funding or other agencies for grant of funds or technical collaboration at the ICMR Headquarters office at New Delhi. All the 26 Institutes under ICMR have their own institutional ethics committees to review the projects undertaken by them for research. ICMR Headquarters IEC will review and approve all types of research proposals involving human participants with a view to safeguard the dignity, rights, safety and well being of all actual or potential research participants. The goals of research, however important, should never be permitted to override the health and well being of the research subjects. The IEC will take care that all the cardinal principles of research ethics viz. Autonomy, Beneficence, Non- maleficience and Justice are taken care of in research protocols. For this purpose, it will look into the aspects of informed consent process, risk benefit ratio, distribution of burden and benefit and provisions for appropriate compensations wherever required. It will review the proposals before start of the studies as well as monitor the research throughout the study until and after completion by examining the annual reports and final reports. The committee will also examine whether all regulatory requirements and laws are complied with or not.


2

3. Composition of IEC 1. Chairman 2. A Basic Scientist 3. Two Clinicians 4. A Lawyer 5. A Social Scientist 6. A Philosopher 7. A lay Person 8. Member Secretary.

4. Authority under which IEC is constituted: The Director-General of ICMR, New Delhi, constitutes ICMR’s Headquarters, IEC. 5. Membership requirements:

a. The members are appointed by the DG, ICMR. b. The members are drawn from different Institutes, and specialties to

give a multisectorial, multidimensional structure. c. The duration of appointment is initially for a period of 3 years d. At the end of 3 years, the committee is reconstituted, and 50% of the

members will be replaced. e. A member can be replaced in the event of death or long-term

assignments outside the country or for any misconduct deemed unfit for a member.

f. A member can tender resignation from the committee with proper reasons to do so, which should be acceptable to the DG, ICMR.

g. All members should maintain absolute confidentiality of all discussions during the meeting.

6. Quorum requirements:

The minimum of 50% + 1 member are required to compose a quorum. All decisions should be taken in meetings and not by circulation of project proposals.


3

7. Offices The Chairperson will conduct all meetings of the IEC. If for reasons beyond control, the Chairperson is not available, an alternate Chairperson will be nominated by the DG from the members present, who will conduct the meeting. The Member Secretary is responsible for organizing the meetings, maintaining the records and communicating with all concerned. He/she will prepare the minutes of the meetings and get it approved by the Chairman before communicating to the researchers with the approval of the DG, ICMR.

8. Independent consultants

IEC may call upon subject experts as independent consultants who may provide special review of selected research protocols, if need be. These experts may be specialists in ethical or legal aspects, specific diseases or methodologies, or represent specific communities, patient groups or special interest groups e.g. Cancer patients, HIV/AIDS positive persons or ethnic minorities. They are required to give their specialized views but do not take part in the decision making process which will be made by the members of the IEC.

9. Applications Procedures:

a. All proposals are to be submitted in the prescribed application form, the details of which are given under Documentation

b. All relevant documents to be enclosed with application form c. 12 copies of the proposal along with the application in prescribed

format to be submitted duly forwarded by the Head of the Division. d. The date of meeting will be intimated to the researcher, to be present,

if necessary to offer clarifications. e. The decision will be communicated in writing. If revision is to be

made, the revised document in 12 copies to be submitted before the next meeting.

10. Documentation:

For a thorough and complete review, all research proposals to be submitted with the following documents : 1. Name of the applicant with designation 2. Name of the Institute/ Hospital / Field area where research will be

conducted. 3. Approval of the Head of the Division


4

4. Protocol of the proposed research 5. Ethical issues in the study and plans to address these issues. 6. Proformae, questionnaires, follow up card, etc. 7. Patient information sheet and informed consent form in local

language. 8. For any drug / device trial, all relevant pre-clinical animal data and

clinical trial data from other countries, if available. 9. Statement describing compensation for study subjects for

participation and/or study related injuries. 10. Curriculum vitae of all the investigators with relevant publications

in last five years. 11. Any regulatory clearances required. 12. Source of funding and financial requirements for the project.. 13. An agreement to report any serious side effects or adverse drug

reactions to IEC. 14. Statement of conflicts of interest, if any. 15. Any other information relevant to the study

11. Review procedures: a. The meeting of the IEC will be held as and when the proposals are

received for review. However, if need be, meetings can be held at scheduled intervals when large number of proposals are to be reviewed..

b. The proposals will be sent to members at least 3 weeks in advance. c. Decisions will be taken by consensus after discussions. d. Researchers will be invited to offer clarifications if need be. e. Independent consultants/Experts will be invited to offer their opinion

on specific research proposals. f. The decisions will be minuted and Chairperson’s approval taken in

writing. 12. Element of review

a. Scientific design and conduct of the study. b. Approval of appropriate scientific review committees. c. Examination of predictable risks/harms. d. Examination of potential benefits. e. Procedure for selection of subjects: Exclusion/ Inclusion criteria f. Management of research related injuries, side effects, ADRs. g. Compensation provisions. h. Justification for placebo in control arm, if any. i. Availability of products after the study, if applicable.


5

j. Patient information sheet and informed consent form in local language.

k. Protection of privacy and confidentiality. l. Involvement of the community, wherever necessary. m. Plans for data analysis and reporting n. Adherence to all regulatory requirements

13. Expedited / Interim review

All revised proposals, unless specifically required to go to the main committee, will be examined in a meeting of identified members convened by the Chairman to expedite decision making. Such expedited review may also be taken up in cases of nationally relevant proposals requiring urgent review

14. Decision-making

a. Members will discuss the various issues before arriving at a consensus

decision. b. Decisions will be made only in meetings where quorum is complete. c. Only members can make the decision. The expert consultants will

only offer their opinions. d. Decision may be to approve, reject or modify the proposals. Specific

suggestions should be given for modifications. e. Modified proposals may be reviewed by an interim review through

identified members. f. Negative decisions should always be substantiated by appropriate

reasons. 15. Communicating the decision

a. Decision will be communicated by the Member Secretary in writing. b. Suggestions of IEC, if any, should be sent for modifications. c. Reasons for rejection should be informed to the researchers. There is

no need to communicate the name of the specific expert or member who made the review.

16. Follow up procedures

a. Regular reports should be submitted for regular review. b. Final report to be submitted at the end of study. c. Any serious side effects, adverse drug reactions and the interventions

undertaken to be intimated. d. Protocol deviation, if any, to be informed with adequate justifications.


6

e. Any new information related to the study should be communicated. f. Premature termination of study should be notified with reasons and

summary of the studies done so far. 17. Archiving/Record keeping

a. Curriculum Vitae (CV) of all members of IEC. b. Copy of all study protocols with enclosed documents, annual reports,

side-effects/ADRS etc. c. Minutes of all meetings with due signature of Chairperson. d. Copy of all existing national and international guidelines on research

ethics. e. Copy of all correspondence with members, researchers and other

regulatory bodies. f. Final report of the approved projects.

18. Updating IEC members

a. All relevant new guidelines to be brought to the attention of the

members. b. Members should be encouraged to attend national and international

training programs in research ethics for maintaining quality in ethical review and to be aware of the latest developments in this area.


INSTITUTIONAL ETHICS COMMITTEE NRI MEDICAL COLLEGE, DOCUMENTS TO BE PRESERVED BY NRI MEDICAL COLLEGE

A) For NRI MC&GH: All documentation and communication of an IEC are to be dated filed and preserved according to written procedures. Strict confidentiality is to be maintained during access and retrieval procedures. Records to be maintained for the followings:

a. The constitution and composition of IEC (decided by Principal) b. The curriculum vitae of NRI MC members c. Standing operating procedures of the IEC d. National and international GCP guidelines including IEC guidelines

(may be kept in library or the WebSite) e. Copies of protocols submitted for review f. All correspondence with IEC members and investigators regarding

application, decision and follow up g. Agenda of all IEC meetings h. Minutes of all IEC meetings with signature of the chairperson i. Copies of decisions communicated to the application j. Record of all notifications issued for premature termination of a

study with a summary of the reasons k. Final report of the study including microfilms, CDs and Video-

recordings. It is recommended that all records must be safely maintained for at least a period of 15 years if it is not possible to maintain the same permanently.

B) For Departments: a. Principal’s circular for composition of NRIMC &GH and changes

done from time to time. b. National and international GCP guidelines including NRIMC&GH

guidelines may be department. c. All applications of your department with copies of protocols and its

annexure submitted to NRIMC &GH for review. d. Copies of NRIMC &GH decisions communicated to applicants of

your department. e. Record of all notifications issued for premature termination of a

study with a summary of the reasons. f. Final report of research studies of your department including

microfilms. CDs and Video-recordings. g. Case record forms an informed consent forms and other documents

of all research projects conducted by students and members of your department.

It is recommended that all records must be safely maintained after the completion or termination of the study for at least a period of 15 years if it is not possible to maintain the same permanently.


Reference for further reading on Ethics

1. National Ethical Guidelines for Biomedical and Health Research involving Human

participants by Indian Council of Medical Research-2017

https://icmr.nic.in/sites/default/files/guidelines/ICMR_Ethical_Guidelines_2017.pdf

2. The Nuremberg Code. Trial of War Criminals before the Nuremberg Military

Tribunals under Control Council Law No.10, Washington DC : US Government

Printing Office, 1949 ; 2:181-182.

3. World medical association declaration of Helsinki. Hongkong:41st world medical

assemble; 1989.

4. Council for international Organizations of medical sciences

(CIOMS).international guidelines of Ethical Review of epidemiological studies.

Geneva : 1991.

5. Council for international organizations of medical sciences (CIOMS).

International guidelines for biomedical research involving human subjects.

Geneva:1993.

6. India council of medical research. Policy statement of ethical considerations

involved in research on human subjects. New Delhi:1980.

7. Council of Ethical and Judicial Affairs. Code of medical Ethics-Current opinions

with annotations. Chicago ; American Medial Association ; 1997 ; 191

8. Office for protection from research risks (OPRR), NIH. Institutional review board

guidebook. United states : Department of Health and human services ; 1993

9. National Commission for the protection of human subjects. Belmont report :

Ethical and guidelines for the protection of human subjects of research.

Washington DC : US Government printing Office; 1978 (Summary and 2 volumes

of appendices)

10. Nuffield council on bioethics. Genetic screening : Ethical issues. U.K: Nuffield

council report; 1993

11. Nuffield council on bioethics. Human tissue : Ethical and Legal issues. U.K :

Nuffield council report; 1995

12. Nuffield council of bioethics, animal-to-human transplants : the Ethics of

xenotransplantation. UK. Nuffield council report; 1996


https://icmr.nic.in/sites/default/files/guidelines/ICMR_Ethical_Guidelines_2017.pdfDr MC DASText BoxFurther reading on Ethics

13. Psychology department. Ethical guidelines for research with human subjects. UK:

University of hertfordshire;1994

14. Network of European CNS transplantation and restoration (NECTAR). Ethical

guideline for the use of human embryonic or fetal tissue for experimental and

clinical neuro-transplantation and research. Netherlands : 1991

15. United Nations educational, Scientific and cultural organization (UNESCO):

UNIVERSAL DECLARATION ON THE HUMAN GENOME AND HUMAN

RIGHTS. International Bioethics committee : 1997

16. Department of biotechnology. Guidelines for gene therapy. New Delhi : 1996

17. Government of India. Exchange of human biological material for biomedical

research, New Delhi: 1997

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Some useful HintsINSTITUTIONAL ETHICS COMMITTEECASE RECORD FORM (CRF) INSTITUTIONAL ETHICS COMMITTEEInvestigator_____________________ Department._______________ Tel.No______Patient’sID___________Age In years____ Sex – M/F Reporting DateDiogonosis_____________________Drug and dose____________________________DateClinical findingsScore1st visitAdverse events monitoringEfficacy parametersSafety parametersSubjectiveLab.TestsSubjectiveLab.Tests12121212• You may use separate case record form for each visit to avoid bias findings of earlier visit. INSTITUTIONAL ETHICS COMMITTEE PATIENTS’ INFORMATION SHEET (PIS)Informed Consent Form (ICF)INSTITUTIONAL ETHICS COMMITTEE INSTITUTIONAL ETHICS COMMITTEEINSTITUTIONAL ETHICS COMMITTEE

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IEC NRIAS Information Broucher2014.pdfSome useful HintsINSTITUTIONAL ETHICS COMMITTEEInformed Consent Form (ICF)INSTITUTIONAL ETHICS COMMITTEECASE RECORD FORM (CRF) Investigator_____________________ Department__________________________________ Mob.No______ Age In years____ Sex – M/F Diogonosis_____________________Drug and dose____________________________DateClinical findingsScore1st visitAdverse events monitoringEfficacy parametersSafety parametersSubjectiveLab.TestsSubjectiveLab.Tests12121212• You may use separate case record form for each visit to avoid bias findings of earlier visit.INSTITUTIONAL ETHICS COMMITTEEPATIENTS’ INFORMATION SHEET (PIS)

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IEC NRI MC & GH Information Brochure2.pdfSome useful HintsINSTITUTIONAL ETHICS COMMITTEECASE RECORD FORM (CRF) Investigator_____________________ Department._______________ Tel.No______Age in years____ Sex – M/F Reporting Date_________________Diogonosis_____________________Drug and dose____________________________DateClinical findingsScore1st visitAdverse events monitoringEfficacy parametersSafety parametersSubjectiveLab.TestsSubjectiveLab.Tests12121212• You may use separate case record form for each visit to avoid bias findings of earlier visit.INSTITUTIONAL ETHICS COMMITTEEPATIENTS’ INFORMATION SHEET (PIS)Informed Consent Form (ICF)INSTITUTIONAL ETHICS COMMITTEE

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nri medical college & gh, nrias information broucher.pdfas per the sop (standard operating...

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